Skip to main content
SpringerLink
Log in

Endocrine therapy testing of human breast cancers in the soft agar clonogenic assay

  • Report
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Summary

The human tumor soft agar cloning assay has been used to assess the biological effects of cytotoxic drugs and other agents on human cancers. In this study we have examined the effects of two hormonal agents, tamoxifen (Tam) and medroxyprogesterone acetate (MPA), on colony growth of the MCF-7 human breast cancer cell line as well as fresh human breast cancer specimens. Using standard criteria for a colony (>50 cells or >60 microns in diameter) Tam (1.0µM) reduced MCF-7 colony formation by only 30% to 50%, and MPA (1.0µM) had no effect. However, both agents dramatically reduced the formation of larger colonies; less than 10% of colonies larger than 124 microns survived Tam exposure, and less than 25% survived with MPA.In vitro sensitivity (< 30% colony survival) of fresh human breast cancer specimens was observed infrequently with either Tam (1/39 evaluable assays) or MPA (3/36 evaluable assays). Colony growth of human breast cancer was unaltered when cells were plated in charcoal-stripped serum to reduce the endogenous estrogen concentration.In vitro sensitivity to Tam or MPA was not increased under these conditions. No correlation was found between estrogen receptor (ER) concentration and inhibition of colony survival with Tam or MPA. None of 16 assays from ER-positive specimens treated with Tam and 2 of 18 ER-positive specimens treated with MPA were sensitivein vitro. In contrast, 2 of 12 ER-negative specimens tested with Tam and 3 of 7 ER-negative specimens tested with MPA were sensitivein vitro. Stimulation of colony growth was observed in about 20% of Tam or MPA-treated specimens. Of the assays with ER data available, 10 of 11 with enhanced colony growth were ER-positive. Human breast cancer specimens did not grow well enough to assess the effect of these agents on large-sized colonies.

These data suggest that the standard human tumor cloning assay will need modification before it can be used to predict hormonal sensitivity of fresh human breast cancer specimens.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abbreviations

ER:

estrogen receptor

PgR:

progesterone receptor

Tam:

tamoxifen

MPA:

medroxyprogesterone acetate

References

  1. Osborne CK, Yochmowitz MG, Knight WA, McGuire WL: The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer 46:2884–2888, 1980

    PubMed  Google Scholar 

  2. Hamburger AW, Salmon SE: Primary bioassay of human tumor stem cells. Science 197:461–463, 1977

    PubMed  Google Scholar 

  3. Von Hoff D, Casper J, Bradley E, Sandbach J, Jones D, Makuck R: Association between human tumor colony-forming assay results and response of an individual patient's tumor to chemotherapy. Am J Med 70:1027–1032, 1981

    PubMed  Google Scholar 

  4. Von Hoff DD, Clark GM, Stogdill BJ, Sarosdy MF, O'Brien MT, Casper JT, Mattox DE, Page CP, Cruz AB, Sandbach JF: Prospective clinical trial of a human tumor cloning system. Cancer Res 43:1926–1931, 1983

    PubMed  Google Scholar 

  5. Soule HD, Vazquez J, Lang A, Albert S, Brennan M: A human cell line from a pleural effusion derived from a breast carcinoma. J Natl Cancer Inst 51:1409–1417, 1973

    PubMed  Google Scholar 

  6. Osborne CK, Bolan G, Monaco ME, Lippman ME: Hormone responsive human breast cancer in long-term tissue culture: effect of insulin. Proc Natl Acad Sci 73:4536–4540, 1976

    PubMed  Google Scholar 

  7. Buick RN: The cell renewal hierarchy in ovarian cancer. In Salmon SE, Trent JM (eds): Human Tumor Cloning. Grune and Stratton, New York, 1984, pp 3–13

    Google Scholar 

  8. Kodama F, Greene GL, Salmon SE: Studies of estrogen receptor expression in MCF-7 cells grown in clonogenic assay. In: Salmon SE, Trent JM (eds): Human Tumor Cloning. Grune and Stratton, New York, 1984, pp 29–35

    Google Scholar 

  9. Sutherland CM, Mather FJ, Carter RD, Cerise EJ, Krementz ET: Breast cancer as analyzed by the human tumor stem cell assay. Surgery 94:370–375, 1983

    PubMed  Google Scholar 

  10. Dittrich C, Sattelhak E, Jokesz R, Kolb R, Holzner H, Havelec L, Lenzhofer R, Steininger R, Vetterlein M, Moser K, Spitzy K-H: Testing of mammary cancer in the human tumor stem cell assay.In Salmon SE, Trent JM (eds): Human Tumor Cloning. Grune and Stratton, New York, 1984, pp 551–556

    Google Scholar 

  11. Jones SE, Dean JC, Young LA, Salmon SE: The clinical usefulness of the human tumor clonogenic assay (HTCA) in breast cancer. In: Salmon SE, Trent JM (eds): Human Tumor Cloning. Grune and Stratton, New York, 1984, pp 557–562

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, University of Texas Health Science Center at San Antonio, 78284, San Antonio, Texas, USA

    C. Kent Osborne, Daniel D. Von Hoff & Kathryn Mullins

Authors
  1. C. Kent Osborne
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel D. Von Hoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kathryn Mullins
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Osborne, C.K., Von Hoff, D.D. & Mullins, K. Endocrine therapy testing of human breast cancers in the soft agar clonogenic assay. Breast Cancer Res Tr 6, 229–235 (1985). https://doi.org/10.1007/BF01806773

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01806773

Key words

Search

Navigation